Current Pharmaceutical Design - Volume 12, Issue 27, 2006

The most fascinating aspect in the process of drug development is the astonishing modification of perspective from which a newly discovered pharmaceutical agent can be viewed. Sometimes it may only be a matter of definition as to whether a pharmaceutical action is labeled as effect or side effect. Primary effects become side effects, and side effects may soon become the new focus of research. One of the most intrigui Read More

Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). Best known as the target of the impotence drug sildenafil, PDE5 degrades cGMP in smooth muscle cells so as to maintain the contracted state of contractile organs such as the penis, blood vessels, uterus, and in Read More

The discovery that inhibition of phosphodiesterase-5 (PDE5) reduces the degradation of cGMP, allowing erectile function to occur by relaxation of penile smooth muscle, represents a revolutionary approach or the treatment of erectile dysfunction (ED). Three PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) are clinically available at this time, and extensive drug design efforts are registered for finding agents with a better activi Read More

Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothelial function and, erection is a basically vascular event that necessitates an intact endothelium to o Read More

Phosphodiesterase 5 inhibitors, such as sildenafil, vardenafil and tadalafil, are now approved for the treatment of erectile dysfunction. They inhibit the cGMP-specific isoform 5 of phosphodiesterase, resulting in cGMP accumulation, which, for example in smooth muscle cells, reduces muscular tone. In the cardiovascular system, they slightly reduce arterial systemic blood pressure. This moderate effect was also shown in combin Read More

In this issue of Current Pharmaceutical Design, new insights and strategies in treating inflammation-related diseases is reviewed by experts. A large number of studies have demonstrated that inflammation plays a critical role in the pathogenesis of various central and peripheral diseases such as age-related neurological disorders, atherosclerosis, sepsis and rheumatoid arthritis. It is well known that the inflammatory reaction is ve Read More

Intercellular adhesion molecule-1 (ICAM-1), an inducible cell adhesion glycoprotein of the immunoglobulin supergene family and cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, are overexpressed by proinflammatory mediators in a wide variety of cell types. These stimuli increase ICAM-1 or COX-2 expression primarily through activation of ICAM-1 or COX-2 gene transcription. The architecture of the ICAM-1 Read More

Increasing evidence indicates that inflammation is involved in the pathogenesis of many neurological, particularly neurodegenerative diseases. Even if inflammation is not a primary causative process, its presence may contribute to the continued loss of CNS neurons. Therefore, it seems reasonable to propose that use of anti-inflammatory drugs might diminish the cumulative effects of inflammation in the brain. Indeed, s Read More

Oxidative stress, in which production of highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) overwhelms antioxidant defenses, is a feature of many neurological diseases and neurodegeneration. ROS and RNS generated extracellularly and intracellularly by various processes initiate and promote neurodegeneration in CNS. ROS and RNS can directly oxidize and damage macromolecules such as DNA, proteins, Read More

The intention of this review is to give a brief overview of the continuously expanding field of sepsis therapy based on recent studies with animal models and clinical trials. Over the past few years, it has become apparent that the mechanisms controlling this disease are more complex than was previously thought, with factors such as free radicals, nuclear factors, and enzyme co-factors all contributing in the control of the p Read More

Nitric oxide (NO) is a reactive radical produced by the enzyme nitric oxide synthase (NOS) and it plays an important role in a large number of biological pathways. NO can be produced under normal physiologic conditions and contribute to homeostasis but, when produced in excess, it may lead to tissue injury and organ dysfunction. The regulation of NOS activity and expression is becoming increasingly understood. NOS enz Read More

A vast amount of circumstantial evidence implicates oxygen-derived free radicals, especially reactive oxygen species and nitric oxide as mediators of inflammation and/or tissue destruction in inflammatory and arthritic disorders. The aim of the current article is to overview the recent developments in this field, as it relates to the roles of nitric oxide (NO) and reactive oxygen species in the pathogenesis of this condition. Read More